The objectives of the research are two-fold: (1) to elucidate the genetic control mechanism of mutagenesis in human and mammalian cells; and (2) to develop reliable in vitro assay systems for environmental mutagens and promoters. We propose (a) to analyze the genetic control of DNA repair and mutagenesis using UV-sensitive or repair deficient Chineses hamster cell mutants isolated by a combined treatment of BrdU-Black light and 3H lethal incorporation; (b) to study the effect of protease inhibitors on mutagenesis and (c) to determine the nature of missense mutations by chemical analysis of the amino acid substitutions in the mutant proteins. We will test the feasibility of using ouabain-resistant mutations and HGPRT metabolic co-operation in Chinese hamster cells for the screening of tumor-promoters. Furthermore, a new mutation assay system using diphtheria toxic resistance as a genetic marker will be developed for human mutation study and for screening of environmental mutagens and carcinogens.